The industrial process of manufacturing tires brings together all the ingredients required to mix a batch of rubber compound in an operation called mixing. The development and use of mixing in a mixing chamber equipped with a rotor has a significant impact on the process itself, and understanding mixing is important in terms of evaluating how material, mixer design, and operating variables (e.g., rpm, temperature, ram pressure) affect distribution, dispersion, and coupling reaction. One of the most important factors to consider is the fill factor, which is the volume of the material relative to the volume of the chamber. It is critical to determine the operating regime in terms of the level of mixing material in the chamber to satisfy all the mixing requirements of the process. Furthermore, the availability of modern high-performance computing resources and accurate mathematical models makes computational fluid dynamics (CFD) an important and necessary tool in understanding some of the complex physical and chemical phenomena associated with such industrial manufacturing problems. The objective of this paper is to assess the effect of fill factor in a two-wing rotor geometry that is used for rubber compounds mixing in the tire manufacturing process and thereby determine the best fill factor with regard to providing the highest mixing efficiency. A series of 3D CFD simulations in a mixing chamber with fill factors of 45, 60, 75, 90, and 100%, stirred by counter-rotating rotors, were carried out using a CFD code. Flow patterns, mixing index, particle trajectories, and statistics such as segregation scale, length of stretch, and pairwise distribution are presented to understand the mixing process with a long-term goal of improving product quality and throughput. Results showed that the major mixing mechanism is shear for most of the fill factors and that the 75% fill factor has the best distributive mixing characteristics among the fill factors studied here.